QUALITATIVE COMMENTS: (with 60 mg) At just over an hour, there was a
sudden blood pressure rise, with the systolic going up 55 mm. This
was maintained for another hour. I found the effects reminiscent of
DET, distinct after-images, and some parasthesia. I was without any
residue by early evening (after 5 hours).

(with 70 mg) It hit quite suddenly. I had a feeling of druggedness,
almost an alcohol-like intoxication, and I never was really high in
the psychedelic sense.

EXTENSIONS AND COMMENTARY: This is another of the essential
amphetamines, because of the appearance of the 4-methoxy group in two
most important essential oils. These are the allylbenzene (estragole
or esdragol) and the propenylisomer (anethole). Their natural
sources have been discussed under TMA.

Two comments are warranted concerning 4-MA, one of scientific
interest, and the other about a social tragedy.

A major metabolites of amphetamine is 4-hydroxyamphetamine, from
oxidation at the 4-position. It has been long known that with chronic
amphetamine usage there is the generation of tolerance, which
encourages ever-increasing doses to be used. When the daily load gets
up around one or two hundred milligrams, the subject can become quite
psychotic. The question was asked: might the chronic amphetamine user
be methylating his endogenously produced 4-hydroxyamphet-amine to
produce 4-methoxyamphetamine (4-MA), and maybe this is the agent that
promotes the psychosis? To address this question, several studies
were done with normal subjects, about 20 years ago, to see if 4-MA
might produce a psychotic state (it didn't at the highest levels
tried, 75 milligrams) and to see if it was excreted to some extent
unchanged in the urines of these normal subjects (it was seen even at
the lowest dosage tried, 10 milligrams). It produced excitation and
other central effects, it produced adrenergic pressor effects, and it
consistently produced measur-able quantities of 4-MA in the urine, but
it produced no amphetamine-like crazies. And since the administration
of up to 600 milligrams of amphetamine produced no detectable 4-MA in
the urine, this theory of psychotomimesis is not valid.

On the tragic side, a few years later, 4-MA became widely distributed
in both the US (as the sulfate salt) and in Canada (as the
hydrochloride), perhaps in-spired by some studies in rats that had
reported that it was second only to LSD in potency as a hallucinogen.
The several deaths that occurred probably followed overdose, and it
was clear that 4-MA was involved as it had been isolated from both
urine and tissue during post mortems. It had been sold under the
names of Chicken Power and Chicken Yellow, and was promoted as being
MDA. I could find no record of a typical street dosage, but comments
collected in association with the deaths implied that the ingested
quantites were in the hundreds of milligrams. Rrecently, the ethoxy
homologue, 4-EA, appeared on the streets of Canada. The dosage,
again, was not reported. It was promptly illegalized there.

The two positional analogues of 4-MA are known; vis., 2-MA and 3-MA.
Their synthesis is straightforward, in imitation of that for 4-MA
above. The meta-compound, 3-MA, has been metabolically explored in
man, but no central effects were noted at a 50 milligram dose (2x25
milligrams, separated by three hours). There appears to be no report
of any human trial of 2-MA. The N-methylhomologue of 2-MA is a
commercial adrenergicbronchodilator called Methoxyphenamine, or
Orthoxine. It has been used in the prevention of acute asthma attacks
in doses of up to 200 milligrams, with only slight central
stimulation. The N-methylhomologues of 3-MA and 4-MA are known, and
the latter compound is the stuff of a separate entry in this book.